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General Information
Name
spastic paraplegia 20
FlyBase ID
FBhh0000035
Disease Ontology Term
Parent Disease
Overview

This report describes spastic paraplegia 20 (SPG20), which is a subtype of spastic paraplegia; SPG20 exhibits autosomal recessive inheritance. This disease is commonly called Troyer syndrome. The human gene implicated in this disease is SPART (Spartin), which encodes a protein containing a MIT (microtubule interacting and trafficking) domain, and is implicated in regulating endosomal trafficking and mitochondria function. There is a single fly ortholog, spartin, for which a classical amorphic allele and RNAi-targeting constructs have been generated.

A UAS construct of the wild-type human gene, Hsap\SPART, has been introduced into flies. Heterologous rescue (functional complementation) has been demonstrated: pan-neuronal expression of this construct rescues larval and adult phenotypes observed for Dmel\spartin mutants.

Animals carrying an amorphic mutation of Dmel\spartin are viable and fertile; observed phenotypes include aspects relevant to spastic paraplegia, such as neuroanatomy defective and locomotor behavior defective. Histological assays using the mutations of the fly gene have allowed characterization of genetic interactions. Physical interaction(s) of the Dmel\spartin protein product have been described; see below and in the gene report for spartin.

[updated Jan 2017 by FlyBase; FBrf0222196]

Disease Summary Information
Parent Disease Summary: spastic paraplegia
Symptoms and phenotype

The hereditary spastic paraplegias (SPG, HSP) are a large group of clinically and genetically diverse disorders characterized by progressive, usually severe, lower extremity spasticity and weakness. SPG is classified by mode of inheritance (autosomal dominant, autosomal recessive, and X-linked) and whether the primary symptoms occur in isolation ('uncomplicated SPG') or with other neurologic abnormalities ('complicated SPG'). [from OMIM:182600; 15.06.29]

Specific Disease Summary: spastic paraplegia 20
OMIM report

[SPASTIC PARAPLEGIA 20, AUTOSOMAL RECESSIVE; SPG20](https://omim.org/entry/275900)

Human gene(s) implicated

[SPARTIN; SPART](https://omim.org/entry/607111)

Symptoms and phenotype

The most common characteristics of SPG20 (Troyer syndrome) are spasticity of the leg muscles, progressive muscle weakness, paraplegia, muscle wasting in the hands and feet (distal amyotrophy), small stature, developmental delay, learning disorders, speech difficulties (dysarthria), and mood swings. [from Genetics Home Reference, GHR_condition:troyer-syndrome, 2015.07.01]

See general description of spastic paraplegia above. SPG20 is a form of complicated SPG. The disorder typically has its onset in early childhood. [from OMIM:275900; 15.07.01]

Genetics

SPG20 (Troyer syndrome) is inherited as an autosomal recessive; it is caused by mutations in the gene SPG20 (spartin). Most described cases are from the Old Order Amish population of Ohio. [from OMIM:275900; 15.07.01]

This form of spastic paraplegia has been reported to occur in two large kindreds, an Amish kindred in the United States and an Arab kindred in Oman. [from NORD: Hereditary Spastic Paraplegia; 2016.09.02]

Cellular phenotype and pathology
Molecular information

SPG20 encodes a protein consisting of an N-terminal MIT (contained in microtubule-interacting and trafficking molecules) domain, a central Eps15-interacting domain, and a C-terminal senescence domain (Ciccarelli et al., 2003, pubmed:12676568; Bakowska et al., 2005, pubmed:16036216).

The SPG20 (spartin) gene shares sequence similarity with the N-terminal region of spastin (SPAST, causative gene of SPG4), as well as with other proteins involved in the morphology and membrane trafficking of endosomes; it has effects upon microtubule dynamics. [from OMIM:607111; 15.07.01]

External links
Disease synonyms
hereditary spastic paraplegia
HSP
spastic paraplegia
SPG
SPG20
Troyer syndrome
Ortholog Information
Human gene(s) in FlyBase
Human gene (HGNC)
Symbol / Name
D. melanogaster ortholog (based on DIOPT)
Comments on ortholog(s)

One to one: 1 human to 1 Drosophila.

Other mammalian ortholog(s) used
    D. melanogaster Gene Information (1)
    Gene Snapshot
    spartin (spartin) encodes a multi-functional protein associated with organelle membranes, including endosomes, lipid droplets, and mitochondria. It participates in cytokinesis, BMP receptor trafficking, lipid droplet turnover, and mitochondrial Ca[2+] homeostasis. [Date last reviewed: 2019-03-14]
    Molecular function (GO)
    Gene Groups / Pathways
    Comments on ortholog(s)

    High-scoring ortholog of human SPART (1 Drosophila to 1 human). Dmel\spartin shares 25% identity and 40% similarity with the human gene.

    Orthologs and Alignments from DRSC
    DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
    Other Genes Used: Viral, Bacterial, Synthetic (0)
      Summary of Physical Interactions (2 groups)
      protein-protein
      Interacting group
      Assay
      References
      anti tag coimmunoprecipitation, anti tag western blot, pull down
      pull down, peptide massfingerprinting, anti tag western blot
      Alleles Reported to Model Human Disease (Disease Ontology) (1 alleles)
      Models Based on Experimental Evidence ( 1 )
      Allele
      Disease
      Evidence
      References
      Modifiers Based on Experimental Evidence ( 1 )
      Allele
      Disease
      Interaction
      References
      model of  Troyer syndrome
      is ameliorated by DadUAS.cTa
      is exacerbated by Eps-15e75
      is ameliorated by witA12
      is exacerbated by Fmr1Δ50M
      is ameliorated by futschK68
      is exacerbated by futschEP1419
      Alleles Representing Disease-Implicated Variants
      Genetic Tools, Stocks and Reagents
      Sources of Stocks
      Contact lab of origin for a reagent not available from a public stock center.
      Bloomington Stock Center Disease Page
      Selected mammalian transgenes
      Allele
      Transgene
      Publicly Available Stocks
      Selected Drosophila transgenes
      Allele
      Transgene
      Publicly Available Stocks
      RNAi constructs available
      Allele
      Transgene
      Publicly Available Stocks
      Selected Drosophila classical alleles
      Allele
      Allele class
      Mutagen
      Publicly Available Stocks
      amorphic allele - molecular evidence
      P-element activity
      References (8)